AN EFFECTIVE SOLVATION TERM BASED ON ATOMIC OCCUPANCIES FOR USE IN PROTEIN SIMULATIONS

Several approaches to the treatment of solvent effects based on continuum models are reviewed and a new method based on occupied atomic volumes (occupancies) is proposed and tested. The new method describes protein-water interactions in terms of atomic solvation parameters, which represent the solvation free energy per unit of volume. These parameters were determined for six different atoms types, using experimental free energies of solvation. The method was implemented in the GROMOS and PRESTO molecular simulation program suites. Simulations with the solvation term require 20-50% more CPU time than the corresponding vacuum simulations and are approximately 20 times faster than explicit water simulations. The method and parameters were tested by carrying out 200 ps simulations of BPTI in water, in vacuo, and with the solvation term. The performance of the solvation term was assessed by comparing the structures and energies from the solvation simulations with the equivalent quantities derived from several BPTI crystal structures and from the explicit water and vacuum simulations. The model structures were evaluated in terms of exposed total surface, buried and exposed polar surfaces, secondary structure preservation, number of hydrogen bonds, energy contributions, and positional deviations from BPTI crystal structures. Vacuum simulations produced unrealistic structures with respect to all criteria applied. The structures resulting from the simulations with explicit water were closer to the 5PTI crystal structure, although part of the secondary structure dissolved. The simulations with the effective solvation term produce structures that are normal according to all evaluations and in most respects are remarkably similar to the 5PTI crystal structure despite considerable positional fluctuations during the simulations. The segments where the model and crystal structures differ are known to be flexible and the observed difference may be physically realistic. The effective solvation term based on occupancies is not only very efficient in terms of computer time but also results in meaningful structural properties for BPTI. It may therefore be generally useful in molecular dynamics of macromolecules.